漆黄素联合胡椒碱的抗抑郁作用及其机制研究

Antidepressant like effect of acute administration with fisetin combined with piperine and its monoamine mechanism

目的探讨低剂量漆黄素(Fisetin)联合阈下剂量胡椒碱的抗抑郁作用是否涉及单胺机制。方法采用行为绝望抑郁模型,即小鼠强迫游泳实验和悬尾实验,观察低剂量漆黄素与阈下剂量胡椒碱急性给药对小鼠绝望模型不动时间的影响,同时观察两药联用对小鼠自主活动的影响。高效液相-电化学检测脑区中单胺递质的含量,荧光分光光度法检测单胺氧化酶(MAO)活性。结果漆黄素(1.25 mg/kg,2.5 mg/kg,5 mg/kg,ig)与阈下剂量胡椒碱2.5 mg/kg·ip联合应用能显著减少小鼠强迫游泳和悬尾实验中的不动时间,且实验剂量范围内药物不影响小鼠的自主活动。低剂量漆黄素与阈下剂量胡椒碱合用能升高海马、皮层和杏仁核中的单胺递质水平同时降低脑内的MAO活性,并且具有统计学意义。结论低剂量漆黄素与阈下剂量胡椒碱联合用药能改善抑郁症样行为,该机制可能是通过抑制单胺氧化酶的活性,从而增加相关的神经递质。

Objective To explore the antidepressant effects of low dose fisetin combined with piperine and its possible mechanism. Methods The tail suspension test and the forced swimming test were used to explore the antidepressant ef-fects of low dose fisetin combined with piperine. In addition, the locomotor activity test was used to exclude the false positive effect in behavioral despair tests. High performance liquid chromatography （HPLC） was used to determine the expression of monoamine. The monoamine oxidase activity in the mouse brain was also determined by fluorospec-trophotometry. Results The results showed that fisetin （1.25 mg/kg, 2.5 mg/kg and 5 mg/kg, ig） combined with piperine （2.5 mg/kg, ip） significantly reduced the duration of immobility in both tail suspension and forced swimming tests. The effective doses did not alter locomotor activity. Moreover, neurochemical assays showed that its produced an increase in monoamine levels in the hippocampus, fronal cortex and amygdala. Monoamine oxidase （MAO） activity in the mouse brain was inhibited while MAO-B activity was not affected. Conclusion These findings suggestde that low dose fisetin combined with piperine exerted antidepressant effect in behavioral despair tests and the underlying mechanism may in-volve the inhibition monoamine oxidase activity in the mouse brain.